Although the etiologies of some secondary cataracts are becoming better understood and certain animal models show promise for elucidating the relationships between lens crystalline and hereditary cataract, little is known about the causes of congenital cataracts in humans. To date, the classification of different congenital cataracts has been cumbersome and imperfect. A better understanding of cataractogenesis will come through an understanding of the molecular components of the lens of the eye and the ways in which lesions of these components are manifested, structurally and functionally, as opacity of the lens. Animal studies have suggested that alterations in lens crystallins can cause hereditary cataracts, making them reasonable candidate genes for causing hereditary cataracts in humans. In addition, it is apparent that hereditary lesions that mimic or contribute additively to environmental stress known to cause cataracts might be candidate genes for causing hereditary cataracts. The work in this project is designed to specifically concentrate on congenital and hereditary cataracts and to take full advantage of molecular technology developed for linkage analysis. Studies performed on informative families will include collecting blood specimens from available family members and, when possible, analyzing lens material from patients who undergo cataract surgery.